Instructions for use Myotil tablets 8 mg No. 14
Composition
active ingredient: thiocolchicoside;
1 tablet contains 8 mg of thiocolchicoside;
Excipients: lactose monohydrate, microcrystalline cellulose (type 101), microcrystalline cellulose (type 102), povidone (type K30), colloidal anhydrous silica, crospovidone (type A), magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: round, biconvex tablets of yellow color.
Pharmacotherapeutic group
Muscle relaxants with a central mechanism of action. ATC code M03B X05.
Pharmacological properties
Pharmacodynamics.
Thiocolchicoside is a semisynthetic muscle relaxant derived from the glycoside colchicoside. It exhibits selective affinity for gamma-aminobutyric acid (GABA) and glycine receptors.
The muscle relaxant effect is manifested mainly at the supraspinal level due to complex regulatory mechanisms; a glycinergic mechanism of action is also not excluded.
The binding of thiocolchicoside to GABA is qualitatively and quantitatively separated from its active metabolite, the glucuronidated derivative.
Thiocolchicoside and its derivatives do not exhibit a sedative effect.
Pharmacokinetics.
Absorption
After intramuscular administration, the maximum plasma concentration (Cmax) of thiocolchicoside is observed after 30 minutes, with values of 113 ng/ml being reached after a 4 mg dose and 175 ng/ml after an 8 mg dose. The corresponding area under the pharmacokinetic concentration-time curve (AUC) are 283 ng∙g/ml and 417 ng∙g/ml.
The pharmacologically active metabolite SL18.0740 is also observed at lower concentrations – with a Cmax of 11.7 ng/ml, which is reached 5 hours after dosing, and an AUC of 83 ng∙g/ml.
There are no data on the inactive metabolite SL59.0955.
The pharmacologically active metabolite SL18.0740 is also detected at lower concentrations with a Cmax of 11.7 ng/ml, achieved 5 hours after dosing, and an AUC of 83 ng.hour/ml. No data are available for the inactive metabolite SL59.0955.
After oral administration of thiocolchicoside, only two metabolites are detected in the blood plasma: the pharmacologically active metabolite SL18.0740 and the inactive metabolite SL59.0955. The maximum plasma concentration of both metabolites of thiocolchicoside is reached after approximately 60 minutes. After a single oral dose of 8 mg, the Cmax and AUC of the metabolite SL18.0740 are approximately 60 ng/ml and 130 ng.h/ml, respectively. The values for the metabolite SL59.0955 are much lower: Cmax is approximately 13 ng/ml and AUC ranges from 15.5 ng.h/ml (up to 3 hours) to 39.7 ng.h/ml (up to 24 hours).
Distribution
The volume of distribution of thiocolchicoside is approximately 42.7 L after administration of 8 mg. Data on the volume of distribution of metabolites are not available.
Metabolism
After oral administration, thiocolchicoside is rapidly metabolized to the aglycone-3-dimethylthiocolchicoside or SL59.0955. This is mainly due to intestinal metabolism, which explains the absence of unchanged thiocolchicoside after oral administration. The metabolite SL59.0955 is glucuronidated to SL18.0740, which has equivalent pharmacological activity to thiocolchicoside and thus provides the pharmacological activity after oral administration of thiocolchicoside. SL59.0955 is also demethylated to dimethylthiocolchicine.
Breeding
After oral administration, 14C-thiocolchicoside is mainly excreted in the feces (79%), with only 20% in the urine. Thiocolchicoside is excreted unchanged in the urine or feces. The metabolites SL18.0740 and SL59.0955 are found in the urine and feces, while didemethylthiocolchicine is excreted only in the feces.
After oral administration of thiocolchicoside, the half-life of metabolite SL18.0740 is 3.2–7 hours and that of metabolite SL59.0955 is on average 0.8 hours.
Indication
Adjunctive therapy for painful muscle contractures in cases of acute spinal pathologies in adults and adolescents aged 16 years and older.
Contraindication
– Hypersensitivity to the active substance or to any of the excipients of the drug;
– pregnancy and breastfeeding;
– use in women of childbearing age who are not using contraception.
Interaction with other medicinal products and other types of interactions
There is no information on interactions. However, caution is recommended when taking Myotil with other muscle relaxants.
When used simultaneously with drugs that depress the central nervous system (CNS), including alcohol, antihypertensive drugs, curare-like drugs, increased muscle relaxation and CNS depression, and the development of hypotension are possible.
When used simultaneously with anticoagulants, the risk of bleeding increases.
Application features
Thiocolchicoside should be used with caution in patients who suffer from epilepsy or who are at increased risk of epileptic seizures.
If epileptic seizures occur, treatment should be discontinued.
In case of diarrhea, the dose should be reduced.
One of the metabolites of thiocolchicoside (SL59.0955) is known to induce aneuploidy (i.e. an unequal number of chromosomes in dividing cells) at concentrations close to those found in human plasma at a dose of 8 mg twice daily orally. Aneuploidy is a risk factor for teratogenicity, embryo-/fetotoxicity, spontaneous abortion, impaired male fertility and the development of cancer. Therefore, the use of the drug in doses exceeding the recommended ones and for prolonged periods should be avoided (see section "Method of administration and dosage").
Women of childbearing age should be informed about the potential risk during pregnancy and the need to use effective contraception.
The medicinal product contains lactose monohydrate, therefore patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Use during pregnancy or breastfeeding
Pregnancy
There is limited information on the use of thiocolchicoside in pregnant women. Therefore, the potential risk to the embryo and fetus is unknown.
Animal studies have shown teratogenic effects (see section "Contraindications").
The drug is contraindicated for use during pregnancy and for women of reproductive potential who are not using adequate contraception.
Breastfeeding period
Since thiocolchicoside passes into breast milk, the drug is contraindicated for use during breastfeeding (see section "Contraindications").
Fertility
Fertility studies in rats showed no changes in fertility at doses up to 12 mg/kg, i.e. at doses that did not cause clinical effects. Thiocolchicoside and its metabolites are aneugenic at various concentrations, which is a risk factor for human fertility.
The ability to influence the reaction speed when driving vehicles or other mechanisms.
There is no data indicating the effect of thiocolchicoside on the ability to drive or use other mechanisms.
During the use of thiocolchicoside, drowsiness may develop, which should be taken into account when driving or operating other mechanisms.
Method of administration and doses
Intended for oral use.
The tablets should be swallowed whole with a glass of water.
The recommended dose is 8 mg every 12 hours (daily dose is 16 mg). The duration of treatment should not exceed 7 consecutive days.
Exceeding the recommended dose or prolonged use should be avoided (see section "Special precautions for use").
Children.
The medicine should not be used in children under 16 years of age.
Overdose
Gastrointestinal reactions such as diarrhea or vomiting are possible.
In case of overdose, careful medical supervision of the patient and symptomatic therapy are recommended.
Adverse reactions
The following adverse reactions are listed by system organ class and frequency: common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000), not known (frequency cannot be estimated from the available data).
On the part of the immune system: very rarely - allergic reactions (urticaria, Quincke's edema); frequency unknown - anaphylactic shock.
Skin and subcutaneous tissue disorders: rarely - vesicular rash; very rarely - itching, erythema, maculopapular rash.
Gastrointestinal: rarely - abdominal pain, diarrhea, nausea and vomiting.
From the nervous system: very rarely - drowsiness; frequency unknown - seizures or recurrence of seizures in patients suffering from epilepsy.
Expiration date
2 years.
Storage conditions
Store at a temperature not exceeding 25 ºС in a place inaccessible to children.
Packaging
14 tablets in a blister, 1 blister in a cardboard box.
Vacation category
According to the recipe.
Producer
Biopharm Sp. z o.o.
Location of the manufacturer and address of its place of business.
Walbrzyska St. 13, Poznań, 60-198, Poland.
