Instructions Thiocolchicoside solution for injection 4 mg/2 ml ampoules 2 ml No. 5
Composition
active ingredient: thiocolchicoside;
1 ampoule (2 ml) of the drug contains thiocolchicoside 4 mg;
Excipients: sodium chloride; sodium citrate; citric acid monohydrate; water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: transparent solution of light yellow color.
Pharmacotherapeutic group
Muscle relaxants. Muscle relaxants with a central mechanism of action. Other centrally acting agents. Thiocolchicoside. ATC code M03B X05.
Pharmacological properties
Pharmacodynamics.
Thiocolchicoside is a semi-synthetic sulfur derivative of colchicoside that has a muscle relaxant effect.
In vitro, thiocolchicoside binds only to strychnine-sensitive GABAergic and glycine-ergic receptors. Since thiocolchicoside acts as a GABAergic receptor antagonist, its muscle relaxant action may be exerted at the supraspinal level by a complex regulatory mechanism, although a glycine-ergic mechanism of action cannot be excluded. The interaction characteristics with GABAergic receptors are qualitatively and quantitatively similar between thiocolchicoside and its main circulating metabolite, the glucuronidated derivative (see section "Pharmacokinetics").
In vivo, the muscle relaxant properties of thiocolchicoside and its main metabolite have been demonstrated in various experimental models in rats and rabbits. The lack of muscle relaxant effect of thiocolchicoside in rats with spinal cord transection indicates a predominant supraspinal activity. In addition, electroencephalographic studies have shown that thiocolchicoside and its main metabolite have no sedative effect.
Pharmacokinetics.
Absorption
After intramuscular administration, Cmax of thiocolchicoside occurs after 30 minutes and reaches values of 113 ng/ml after a 4 mg dose and 175 ng/ml after an 8 mg dose. The corresponding AUC values are 283 and 417 ng×h/ml, respectively.
The pharmacologically active metabolite SL18.0740 is also detected – at lower concentrations, with a Cmax of 11.7 ng/ml achieved 5 hours after administration, and an AUC of 83 ng×h/ml.
There are no data on the inactive metabolite SL59.0955.
Distribution
The apparent volume of distribution of thiocolchicoside is approximately 42.7 L after intramuscular administration of 8 mg. There are no data on metabolites.
Breeding
After intramuscular administration, the apparent T½ of thiocolchicoside is 1.5 hours, and the plasma clearance is 19.2 l/h.
Indication
Adjunctive therapy for painful muscle contractures in acute spinal diseases in adults and adolescents aged 16 years and older.
Contraindication
Thiocolchicoside should not be used:
- patients with hypersensitivity to the active substance or to any of the excipients;
- throughout the entire period of pregnancy;
- during breastfeeding;
- women of reproductive age who do not use contraceptives;
- patients with flaccid paralysis, muscle hypotension.
Interaction with other medicinal products and other types of interactions
Interaction studies have not been conducted.
Application features
After intramuscular administration, episodes of vasovagal syncope have been observed, therefore the patient should be monitored after injection (see section "Adverse reactions").
Cases of liver injury have been reported during post-marketing use of thiocolchicoside. Serious cases (e.g. fulminant hepatitis) have been reported in patients taking concomitant non-steroidal anti-inflammatory drugs or paracetamol. Patients should be advised to discontinue treatment and seek medical advice if they develop signs and symptoms of liver injury (see section 4.8).
Thiocolchicoside may cause seizures, especially in patients with epilepsy or those at risk of developing seizures (see section "Adverse reactions").
The maximum recommended dose of thiocolchicoside of 8 mg per day should not be exceeded, which should be divided into 2 doses with an interval of 12 hours. If a dose of the drug is missed, the next dose should be taken as soon as possible, avoiding double doses.
In preclinical studies, one of the metabolites of thiocolchicoside (SL59.0955) caused aneuploidy (changes in the number of chromosomes in dividing cells) at concentrations close to the human exposure observed at oral doses of 8 mg twice daily. Aneuploidy is considered a risk factor for teratogenicity, embryo/fetal toxicity, miscarriage, impaired male fertility and a potential risk factor for cancer. As a precautionary measure, higher than recommended doses or prolonged use should be avoided (see section 4.2).
Patients should be carefully informed about the potential risk of possible pregnancy and the need for effective contraceptive measures to be followed.
Important information about excipients
This medicinal product contains less than 1 mmol (23 mg) sodium/dose, i.e. essentially sodium-free.
Use during pregnancy or breastfeeding
Data on the use of thiocolchicoside in pregnant women are limited. Therefore, the potential risks to the embryo and fetus are unknown.
Animal studies have shown teratogenic effects.
The drug is contraindicated in pregnant women and women of reproductive age who do not use contraceptives (see section "Contraindications").
Breast-feeding
The use of thiocolchicoside is contraindicated during breastfeeding, as it is excreted in breast milk (see section "Contraindications").
Fertility
In a fertility study in rats, no impairment of fertility was observed at doses up to 12 mg/kg, i.e. at dose levels that did not cause a clinical effect. Thiocolchicoside and its metabolites exhibit aneugenic effects at various concentration levels, which is a risk factor for impairment of human fertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies on the ability to drive or use machines have been conducted.
Since drowsiness is a common occurrence, this should be taken into account when driving or operating machinery.
Method of administration and doses
The drug is intended for intramuscular administration. The recommended and maximum dose is 4 mg intramuscularly every 12 hours (8 mg per day). The duration of treatment is limited to 5 consecutive days.
Higher than recommended dosages or prolonged use should be avoided (see section "Special precautions for use").
Children.
The drug is contraindicated for use in children under 16 years of age.
Overdose
Cases of overdose are unknown.
In case of overdose of the drug, careful medical supervision of the patient and the use of symptomatic therapy are recommended.
Side effects
The following adverse reactions are listed according to MedDRA [Medical Dictionary for Regulatory Activities] system organ classes and frequencies: very common (≥ 1/10), common (≥ 1/100 - < 1/10), uncommon (≥ 1/1,000 - < 1/100), rare (≥ 1/10,000 - < 1/1,000), very rare (< 1/10,000), frequency not known (cannot be estimated from the available data).
Immune system disorders
Uncommon: itching.
Rare: urticaria.
Very rare: hypotension.
Frequency unknown: angioedema and anaphylactic reactions, including anaphylactic shock.
Nervous system disorders
Common: drowsiness.
Rare: agitation or short-term confusion.
Frequency unknown: malaise, with or without vasovagal syncope a few minutes after intramuscular injection, convulsions (see section "Special warnings and precautions for use").
Gastrointestinal disorders
Common: diarrhea, gastralgia.
Uncommon: nausea, vomiting.
Rare: heartburn.
Hepatobiliary disorders
Frequency unknown: drug-induced liver damage (see section "Special warnings and precautions for use").
Skin and subcutaneous tissue disorders
Uncommon: allergic skin reactions.
Reporting of suspected adverse reactions
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua.
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Incompatibility.
Extemporaneous mixing in the syringe of the drug with parenteral administration agents containing tenoxicam, piroxicam, ketoprofen, ketorolac tromethamine, diclofenac sodium, lysine acetylsalicylate, betamethasone disodium phosphate, cyanocobalamin (vitamin B12) and a complex of vitamins B1, B6 and B12 is possible.
Packaging
2 ml in ampoule No. 5 (5x1), No. 10 (10x1) in a blister in a box.
Vacation category
According to the recipe.
Producer
Limited Liability Company "Pharmaceutical Company "Zdorovya".
Location of the manufacturer and address of the place of its activity. Ukraine, 61013, Kharkiv region, Kharkiv city, Shevchenko street, building 22.
