Baclofen tablets 25 mg No. 50

Instructions for use Baclofen tablets 25 mg No. 50

Composition

active ingredient: baclofen;

1 tablet contains 25 mg of baclofen;

excipients: lactose monohydrate, potato starch, gelatin, talc, magnesium stearate, ethyl cellulose.

Dosage form

Pills.

Main physicochemical properties:

25 mg tablets: white, round, biconvex.

Pharmacotherapeutic group

Centrally acting muscle relaxants. ATX code M03B X01.

Pharmacological properties

Pharmacodynamics

Baclofen is a muscle relaxant that acts at the spinal cord level; a derivative of gamma-aminobutyric acid (GABA). From a chemical point of view, baclofen does not belong to other muscle relaxants.

Baclofen reduces the increased muscle tone caused by spinal cord injury. The drug simultaneously and equally suppresses skin reflexes and muscle tone, while only slightly reducing the amplitude of tendon reflexes.

The mechanism of action is most likely to involve hyperpolarization of ascending nerves and inhibition of both mono- and polysynaptic reflexes at the spinal cord level by stimulation of GABAB receptors, thereby blocking the release of the amino acids glutamate and aspartate. Baclofen does not affect neuromuscular transmission.

In animal experiments, baclofen increased dopamine metabolism, but in humans, the concentration of 5-hydroxyindole acetate or dopamine metabolites in the cerebrospinal fluid did not change under the influence of the drug.

Since baclofen in large doses can suppress CNS functions, there is a possibility that the drug may act on centers located above the spinal cord.

The benefits of baclofen are related to its ability to reduce painful flexor spasms and spontaneous muscle contractions, thereby improving the patient's mobility and reducing dependence on the help of other people, improving rehabilitation. Baclofen also reduces pain sensitivity. Thus, improving the patient's general well-being and sedation is less difficult than with other drugs that affect the CNS.

Baclofen stimulates gastric secretion.

Pharmacokinetics

Absorption

Baclofen is rapidly and almost completely absorbed from the gastrointestinal tract.

There are no significant differences in Tmax, Cmax, and bioavailability between the solution and solid dosage forms of baclofen. After oral administration of a single dose (10–30 mg), peak plasma concentrations are reached within 0.5–1.5 hours, and the area under the concentration curve is proportional to the dose.

The extent of absorption decreases with higher doses.

The therapeutic concentration is 80–395 ng/mL.

Animal experiments have shown that baclofen is distributed in many tissues, but only a small portion of it penetrates the blood-brain barrier.

In patients, the maximum concentration (Cmax 500–600 ng/ml) is reached 2–3 hours after administration, and the concentration above 200 ng/ml is maintained for 8 hours.

Distribution

Baclofen crosses the placental barrier.

A minimal amount of the drug penetrates into breast milk.

The volume of distribution of baclofen is 0.7 l/kg, and the binding to plasma proteins is approximately 30%, this level remains unchanged at baclofen concentrations from 10 ng/ml to 300 μg/ml. In the cerebrospinal fluid, the concentration of the active substance is 8.5 times lower than in blood plasma.

Biotransformation

Approximately 15% of the administered dose undergoes biotransformation in the liver by deamination. Deamination results in the formation of the main metabolite, β-(p-chlorophenyl)-4-hydroxybutyric acid, which does not exhibit pharmacological activity.

Breeding

The half-life is 3–4 hours.

Baclofen is excreted in the urine, 70–80% as unchanged drug or metabolites. The remainder is excreted in the feces.

When administered orally, baclofen is almost completely eliminated within 72 hours.

Elderly patients

The pharmacokinetics in elderly patients are almost the same as in adults. The maximum plasma concentration of baclofen is slightly lower than in healthy young volunteers, but the AUC is similar in both groups of patients.

Children

In children (2-12 years of age) after administration of baclofen 2.5 mg tablets, the Cmax is 62.8±28.7 ng/mL and the Tmax is 0.95-2 hours. The mean plasma clearance (Cl) has been reported to be 315.9 mL/h/kg, the volume of distribution (Vd) to be 2.58 L/kg, and the elimination half-life (T1⁄2) to be 5.1 hours.

Patients with hepatic insufficiency

Pharmacokinetic data on the use of baclofen in patients with hepatic insufficiency are not available. However, since the liver does not play a significant role in the transformation and excretion of baclofen, clinically significant changes in the pharmacokinetics of baclofen in patients with hepatic insufficiency are not expected.

Controlled clinical studies of the pharmacokinetics of baclofen in patients with renal insufficiency have not been conducted. The main part of baclofen was excreted in the urine in unchanged form. There are limited data, according to which the concentration of the drug in the blood plasma in patients on continuous hemodialysis and patients with compensated renal insufficiency indicates a significant decrease in clearance and an increase in the half-life in these groups. Patients with impaired renal function should adjust the dose of the drug depending on the level of baclofen in the systemic circulation, immediate hemodialysis is an effective method of removing excess baclofen from the systemic circulation.

Indication

Spastic states during:

multiple sclerosis; other spinal cord lesions (e.g., spinal cord tumors, syringomyelia, motor neuron disease, lumbar myelitis, spinal cord injuries); cerebral strokes; cerebral palsy; inflammation of the spinal and brain membranes; head injuries.

Children

Baclofen is used in children for the symptomatic treatment of spastic conditions of cerebral genesis resulting from cerebral palsy, as well as from cerebral vascular incidents due to neoplasms or degenerative brain diseases.

Baclofen is also indicated for the symptomatic treatment of muscle spasticity resulting from spinal cord infections and diseases, degenerative changes, trauma, neoplasms and lesions of unknown origin, such as multiple sclerosis, amyotrophic lateral sclerosis, syringomyelia, lumbar myelitis, traumatic injury, lower paraparesis or spinal cord compression.

Contraindication

Hypersensitivity to baclofen or to any of the excipients of the drug. Gastric and duodenal ulcer in the acute stage. Porphyria.

Interaction with other medicinal products and other types of interactions

Concomitant use of baclofen with other drugs that depress CNS activity, such as other muscle relaxants (tizanidine), synthetic opiates, or alcohol, enhances their sedative effect.

Patients receiving baclofen are at increased risk of respiratory depression. In addition, hypotension has been reported with concomitant use of morphine and intrathecal baclofen. Cardiac and respiratory function should be closely monitored, especially in patients with concomitant vascular and respiratory disease and respiratory muscle weakness.

Baclofen may increase hyperkinesia in patients taking lithium salts concomitantly.

Tricyclic antidepressants can potentiate the effects of baclofen and significantly reduce muscle tone.

Baclofen potentiates the effect of antihypertensive agents (dosage adjustment may be necessary).

Drugs that affect kidney function (e.g. ibuprofen) slow down the elimination of baclofen, which is the cause of symptoms of poisoning (see section "Special instructions").

In patients with Parkinson's disease taking levodopa and carbidopa, confusion, hallucinations, nausea, and mental agitation may occur when combined with baclofen. Exacerbation of parkinsonism has been reported. Therefore, caution should be exercised when baclofen is used concomitantly with levodopa or carbidopa.

Baclofen enhances analgesia induced by fentanyl.

Application features

Mental disorders and nervous system disorders

During treatment with baclofen, psychotic syndromes, schizophrenia, depressive or manic disorders, convulsive states, dizziness, and symptoms of parkinsonism are exacerbated, so the drug should be used with caution, and the patient should be under constant medical supervision.

Cases of suicide and suicidal behaviour have been reported in patients treated with baclofen. In most cases, patients had additional risk factors associated with an increased risk of suicide, including alcohol use disorders, depression and/or a history of suicide attempts. Patients with additional risk factors should be under close medical supervision while receiving baclofen. Patients (and caregivers of patients) should be warned about the use of baclofen and the need to monitor for clinical worsening, suicidal behaviour or thoughts, or unusual changes in behaviour and to seek medical advice immediately if these occur.

Cases of misuse, abuse and dependence have been reported during treatment with baclofen. Caution should be exercised when prescribing to patients with a history of abuse and monitoring for signs of misuse, abuse and dependence during treatment with baclofen, such as dose escalation, behaviour indicative of manipulation to obtain the drug, development of habituation.

Epilepsy

Patients with epilepsy who require concomitant baclofen therapy require constant clinical monitoring and EEG monitoring, as a decrease in the effectiveness of the anticonvulsant drugs used and changes in the EEG pattern have been noted.

Caution should be exercised when using baclofen in patients in whom maintaining upright posture and balance or increasing range of motion depends on marked muscle tension.

Baclofen should be prescribed with particular caution to patients taking antihypertensive drugs (interactions may occur) (see section “Interaction with other medicinal products and other types of interactions”).

The drug should be used with caution in patients with stroke, respiratory function disorders, and liver function disorders.

Renal disorders

Baclofen is excreted in the urine, mainly unchanged, so the drug should be prescribed with caution to people with impaired renal function. The dose of the drug should be reduced in these patients. In patients with end-stage renal failure (CKD - stage 5, GFR < 15 ml/min), baclofen should be used only if the potential benefit outweighs the risk (see section "Method of administration and dosage").

Neurological symptoms of overdose, including clinical manifestations of toxic encephalopathy (e.g. confusion, disorientation, drowsiness and depressed consciousness) have been observed in patients with renal impairment who have received oral baclofen at doses above 5 mg/day. Patients with renal insufficiency should be closely monitored for early detection of toxicity.

Particular caution should be exercised when using baclofen in combination with other drugs that affect renal function. Renal function should also be carefully monitored and the daily dose of baclofen should be adjusted to avoid toxicity.

Cases of baclofen poisoning have been reported in patients with acute renal failure (see section "Overdose").

In addition, after discontinuation of treatment, hemodialysis may be an alternative treatment for patients poisoned by baclofen. Hemodialysis effectively removes baclofen from the body, reduces the manifestation of clinical symptoms of overdose and accelerates the recovery of patients.

Urinary tract disorders

Caution should be exercised in patients with increased bladder sphincter tone (possible urinary retention).

Improvement in the condition after the use of baclofen is observed in patients with neurogenic bladder emptying disorder.

Laboratory studies

Some patients treated with baclofen have been observed to have increased levels of aspartate aminotransferase, alkaline phosphatase and serum glucose. Laboratory monitoring is recommended, especially in patients with impaired liver function and diabetes mellitus.

Sudden cancellation

During sudden withdrawal of the drug (especially after a long period of treatment), anxiety and confusion, hallucinations, psychotic reactions, manic, paranoid and convulsive states, dyskinesias, tachycardia, hyperthermia, rhabdomyolysis may occur, and spastic states may also increase, so the dose of the drug should be reduced gradually, over 1–2 weeks.

Patients aged 65 years and over

Particular caution should be exercised when treating elderly patients (increased risk of side effects).

Excipients

The medicinal product should not be used in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

Ability to influence reaction speed when driving vehicles or other mechanisms

Baclofen may cause dizziness, sedation, drowsiness and visual disturbances (see section "Adverse reactions"), which may impair concentration and alertness. Patients experiencing these adverse reactions should not drive or operate machinery.

Use during pregnancy or breastfeeding

There are no controlled studies on the use of the drug in pregnant women. Baclofen crosses the placental barrier.

Baclofen can be used during pregnancy (especially in the first trimester of pregnancy) only if the benefit to the pregnant woman outweighs the possible risk to the fetus.

There has been only one case of withdrawal syndrome (convulsions) in a 7-day-old neonate whose mother had taken baclofen 80 mg/day during pregnancy. The seizures, which were treated with standard anticonvulsants, resolved within 30 minutes of baclofen administration.

Baclofen passes into breast milk, but if the drug is taken in therapeutic doses in extremely small quantities, adverse reactions in the newborn are not expected.

Method of administration and doses

The dose is set individually, determining the lowest effective dose that does not cause side effects.

The drug should be taken with meals.

If the therapeutic effect is not achieved after 6 weeks of treatment at the maximum recommended doses, the issue of prolonging/discontinuing treatment with the drug should be considered.

Discontinuation of treatment should always be carried out gradually, reducing the dose over a period of 1–2 weeks, except in emergencies related to overdose or the occurrence of serious adverse reactions.

The following dosage regimen is recommended.

Adults

Treatment should be initiated with a daily dose of 15 mg, divided into several equal doses. The following scheme of gradual dose increase is suggested, but the individual characteristics of each patient should always be taken into account:

in the first 3 days, 5 mg (1/2 tablet of 10 mg) 3 times a day,

for the next 3 days – 1 tablet of 10 mg 3 times a day,

for the next 3 days – 1 ½ tablets of 10 mg 3 times a day,

for the next 3 days – 2 tablets of 10 mg 3 times a day.

In most patients, the therapeutic effect occurs at a dose of 30 mg to 75 mg per day.

The above-mentioned regimen ensures good tolerability of the drug.

If necessary, the dose can be carefully increased.

Patients who need to take higher doses of the drug (75–100 mg per day) can use baclofen in the form of 25 mg tablets.

Do not exceed a dose of 100 mg per day.

The duration of treatment depends on the patient's clinical condition.

Baclofen treatment should not be stopped abruptly due to the risk of hallucinations and exacerbation of spastic conditions.

Elderly patients

For elderly patients, the dose of the drug should be increased with special caution due to the increased risk of side effects.

Children

Treatment should be initiated with a very low dose (corresponding to a dose equivalent to approximately 0.3 mg/kg body weight per day), administered in 2–4 divided doses (preferably 4 equal doses).

For children, the dose should be increased with caution, at one-week intervals, until the optimal therapeutic effect is achieved.

In general, the daily dose of maintenance therapy should be 0.75–2 mg/kg body weight.

The maximum daily dose should not exceed 40 mg for children under 8 years of age. For children over 8 years of age, the maximum daily dose is 60 mg.

Baclofen in tablet form should not be prescribed to children weighing less than 33 kg.

Patients with renal impairment

For such patients, as well as for patients on dialysis, the recommended doses should be reduced to 5 mg per day.

Baclofen may be used in patients with end-stage renal disease when the potential benefit outweighs the risk. Such patients should be monitored for symptoms of early toxicity (such as drowsiness, coma) (see sections 4.4 and 4.8).

Patients with spastic conditions of cerebral origin

Adverse effects are observed most frequently in this group of patients, therefore the dosage regimen should be established accordingly for these patients and they should be under close medical supervision.

Children

Baclofen in tablet form should not be prescribed to children weighing less than 33 kg.

For information on use in children, see the section “Method of administration and dosage”.

Overdose

In case of an overdose of the drug, the following side effects from the CNS may develop: drowsiness, loss of consciousness, coma, respiratory depression.

Other symptoms may occur, such as: states of confusion, hallucinations, mental agitation, accommodation disorders, absence of pupillary reflexes, muscle hypotension, clonic convulsions, depression or absence of reflexes, convulsions, changes in EEG (suppression of bursts and triphasic waves), peripheral vasodilation, arterial hypotension or hypertension, bradycardia, tachycardia or tachyarrhythmia, hypothermia, nausea, vomiting, diarrhea, excessive salivation, increased activity of lactate dehydrogenase, aspartate aminotransferase and alkaline phosphatase.

In patients with renal insufficiency, symptoms of overdose may occur when using lower doses of baclofen (see sections “Method of administration and dosage” and “Special precautions for use”).

The general condition may worsen in patients who are simultaneously using other drugs and substances that affect the central nervous system (e.g. alcohol, diazepam, tricyclic antidepressants).

Treatment

There is no specific antidote.

Symptomatic treatment should be used, aimed at eliminating complications associated with arterial hypotension, arterial hypertension, convulsions, depression of the nervous system or circulatory system.

Induce vomiting or perform gastric lavage as soon as possible, and administer activated charcoal.

Comatose patients should be intubated before gastric lavage.

If necessary, use saline laxatives.

For patients with respiratory arrest, perform artificial respiration and ensure cardiovascular support.

Some published data indicate that in milder poisonings, physostigmine given intravenously (1–2 mg over 5–10 minutes) reverses CNS side effects, especially drowsiness and respiratory depression. If there is no improvement after the first dose of physostigmine, a second dose can be given after 30–60 minutes.

In case of severe poisoning, hemodialysis may be prescribed for patients with renal failure (see section "Special instructions").

If convulsions occur, diazepam should be administered intravenously with great caution.

Adverse reactions

Adverse effects are most often observed at the beginning of treatment (e.g. drowsiness and nausea), during rapid dose increases or use of high doses of baclofen, and in elderly patients.

They are mostly transient and disappear after dose reduction. In case of severe adverse reactions, the drug should be discontinued.

If nausea persists after reducing the dose, it is recommended to take baclofen with food or milk.

In patients with a history of mental illness or cerebrovascular disease (e.g. stroke), as well as in elderly patients, undesirable effects may occur with more serious consequences.

A lowering of the seizure threshold and seizures are possible, especially in patients with epilepsy.

Some patients have experienced increased spasticity as a paradoxical reaction to the drug.

Unfavorable muscular hypotension may occur, making it difficult for patients to walk or care for themselves and can usually be alleviated by re-evaluating the dosage regimen (i.e., by reducing daytime doses and increasing the evening dose).

The following undesirable effects have been observed during the use of baclofen:

*When using baclofen in high doses (≥ 100 mg) in patients with alcohol dependence, cases of sleep apnea syndrome have been observed.

Some patients experienced increased spasticity (a paradoxical reaction to the drug).

The undesirable degree of muscle tension that may occur, causing difficulty for patients when walking or performing self-care, usually resolves after dosage adjustments (e.g., by reducing the doses used during the day but increasing the evening dose).

Expiration date

3 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging

50 tablets in a polyethylene bottle (HDPE) with a cap (LDPE) with a shock absorber and a protective ring, 1 bottle in a cardboard box.

Vacation category

According to the recipe.

Producer

Pharmaceutical Plant "Polpharma" S.A., Poland.

Location of the manufacturer and its business address

St. Pelplinski 19, 83-200, Starogard Gdański, Poland.