TIKOSID

INSTRUCTIONS for medical use of the medicinal product TIKOZID (TIKOZID)

Composition:

Active substance: thiocolchicoside;

1 ampoule (2 mL) contains thiocolchicoside 4 mg;

Excipients: sodium chloride, diluted hydrochloric acid, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear light yellow solution.

Pharmacotherapeutic group.
Muscle relaxants with central mechanism of action. ATC code M03BX05.

Pharmacological Properties.

Pharmacodynamics.

Thiocolchicoside is a semi-synthetic sulfide derivative of colchicoside with myorelaxant activity.

In vitro studies show that thiocolchicoside binds only to GABA and strychnine-sensitive glycine receptors. Thiocolchicoside exhibits selective affinity for GABA receptors and produces an effective myorelaxant effect through regulatory complex mechanisms at different levels of the nervous system; however, its glycine-mediated mechanism of action cannot be excluded.

The characteristics of thiocolchicoside interaction with GABA receptors are the same as those of its glucuronide derivative, which is the main metabolite (see below).

In vivo studies have demonstrated the myorelaxant properties of thiocolchicoside and its main metabolite in various experimental models.

Electroencephalographic studies also showed that thiocolchicoside and its major metabolite do not produce a sedative effect.

Pharmacokinetics.

Absorption.

After intramuscular administration, maximum plasma concentration (Cmax) of thiocolchicoside is reached within 30 minutes. Plasma levels of 113 ng/mL are achieved after a 4 mg dose, and 175 ng/mL after an 8 mg dose. Corresponding area under the pharmacokinetic curve (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 reached 5 hours after dosing, and AUC of 83 ng·h/mL.

Data on the inactive metabolite SL59.0955 are not available.

Distribution.

The apparent volume of distribution of thiocolchicoside is approximately 42.7 L after intramuscular administration of 8 mg. Data on both metabolites are not available.

Elimination.

The elimination half-life of thiocolchicoside is 1.5 hours, and plasma clearance is 19.2 L/h.

Clinical characteristics.

Indications.

Additional therapy for painful muscular contractures in cases of acute spinal disorders in adults and adolescents aged 16 years and older.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients of the medicinal product;
• flaccid paralysis, muscle hypotonia;
• pregnancy;
• breastfeeding period;
• use in women of childbearing potential who are not using appropriate contraceptive measures during treatment and for one month after completion of treatment;
• use in men who are not using appropriate contraceptive measures during treatment and for three months after completion of treatment.

Interaction with other medicinal products and other forms of interaction.

Information on interactions is lacking.

Special precautions for use

After intramuscular injection of thiocolchicoside, cases of vasovagal syncope have been reported; therefore, patients should be monitored after administration of the medicinal product (see section "Adverse reactions").

During the post-marketing period, liver injury associated with the use of thiocolchicoside has been reported. Severe cases (e.g., fulminant hepatitis) of liver injury have been observed in patients who concurrently used non-steroidal anti-inflammatory drugs or paracetamol. If signs of liver injury occur during treatment with the medicinal product, therapy should be discontinued and medical advice should be sought (see section "Adverse reactions").

Epileptic seizures may occur during treatment with thiocolchicoside in patients suffering from epilepsy or from conditions associated with a risk of seizures (see section "Adverse reactions").

The maximum recommended daily dose of thiocolchicoside (8 mg) should not be exceeded. This dose should be divided into two administrations with a 12-hour interval. If a dose is missed, the next dose should be administered at the usual time.

According to data from preclinical studies, one of the metabolites of thiocolchicoside, SL59.0955, causes aneuploidy (alteration in the number of chromosomes in dividing cells) at concentrations close to those achieved with 8 mg twice daily orally, which may similarly affect humans.

Aneuploidy is considered a risk factor for teratogenicity, embryotoxicity/fetotoxicity, miscarriage, altered fertility in men, and a potential risk factor for carcinogenesis. As a precaution, exceeding the recommended dose or prolonged use of the medicinal product should be avoided (see section "Dosage and administration").

Patients should be adequately informed about the potential risks for possible pregnancy and about the effective contraceptive methods that should be used.

Following intramuscular administration of thiocolchicoside, injection site reactions have been reported, including necrosis at the injection site and cutaneous oil embolism, also known as Nicolau syndrome, and livedoid dermatitis (see section "Adverse reactions"). Proper injection technique must be followed when administering thiocolchicoside intramuscularly.

The medicinal product contains less than 1 mmol (23 mg) of sodium per dose, i.e., it is practically sodium-free.

Pregnancy and breastfeeding.

Contraception in women and men.

The medicinal product is contraindicated in women of childbearing potential and in men who do not use effective contraceptive methods (see section "Contraindications").

Due to the aneugenic potential of thiocolchicoside and its metabolites, women of childbearing potential must use effective contraception during treatment with thiocolchicoside and for one month after completion of treatment.

Men must use effective contraception during treatment with thiocolchicoside and for three months after completion of treatment (see section "Contraindications").

Pregnancy

Information on the use of thiocolchicoside in pregnant women is limited, and therefore the potential risk to the embryo and fetus is unknown. Animal studies have shown teratogenic effects of thiocolchicoside. The medicinal product is contraindicated during pregnancy (see section "Contraindications").

Breastfeeding

Thiocolchicoside passes into breast milk. The medicinal product is contraindicated during breastfeeding (see section "Contraindications").

Fertility

Thiocolchicoside and its metabolites exhibit aneugenic effects at various concentration levels, which represents a risk factor for human fertility.

Ability to influence the speed of reactions when driving or operating machinery

Studies on the effect of thiocolchicoside on the ability to drive or operate machinery have not been conducted.

Somnolence may occur during treatment with thiocolchicoside, which should be taken into account when driving or operating machinery.

Dosage and Administration

The medicinal product is intended for intramuscular administration.

The recommended maximum daily dose is 4 mg every 12 hours (8 mg per day).

Treatment should not exceed 5 consecutive days.

Exceeding the recommended dose or duration of use should be avoided (see section "Special Warnings and Precautions for Use").

Children

The medicinal product is contraindicated for use in children under 16 years of age.

Overdose

There are no data regarding cases of overdose. In the event of overdose, careful medical monitoring of the patient and symptomatic therapy are recommended.

Adverse reactions.

The adverse reactions listed below are systematized according to MedDRA system organ classes and frequency: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000), unknown (frequency cannot be estimated from available data).

Immune system disorders:

uncommon – pruritus; rare – urticaria; very rare – hypotension; unknown – angioedema and anaphylactic reactions, including anaphylactic shock.

Nervous system disorders:

common – drowsiness; rare – excitement or brief confusion; unknown – malaise, with or without vasovagal syncope within the first few minutes after intramuscular injection; seizures (see section "Special precautions for use").

Gastrointestinal disorders:

common – diarrhea, stomach pain; uncommon – nausea, vomiting; rare – heartburn.

Hepatobiliary disorders:

frequency unknown – liver injury (see section "Special precautions for use").

Skin and subcutaneous tissue disorders:

uncommon – allergic skin reactions.

General disorders and administration site conditions:

unknown – injection site reactions, including swelling, erythema, pruritus, pain around the injection site, and Nicolau syndrome ("pharmacological embolism of the skin" and "livedoid dermatitis") following intramuscular injection.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 25 °C in the original packaging and in a place inaccessible to children.

Packaging.

2 ml in an ampoule; 6 ampoules in a blister pack; 1 blister pack in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

WORLD MEDICINE ILAC SAN. VE TIC. A.S. /
WORLD MEDICINE ILAC SAN. VE TIC. A.S.

Manufacturer's address and place of business.

COSB G.O.Pasa Mah. 6. Cad. No:30, Cerkezkoy/Tekirdag, Turkey /
COSB G.O.Pasa Mah. 6. Cad. No:30, Cerkezkoy/Tekirdag, Turkey.

Marketing authorization holder.

WORLD MEDICINE, LLC, Ukraine /
WORLD MEDICINE, LLC, Ukraine.