Thiovista

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT THIOVISTA (THIOVISTA)

Composition:

active substance: thiocolchicoside;

1 ampoule contains thiocolchicoside 4 mg;

excipients: sodium chloride, hydrochloric acid, sodium hydroxide, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical characteristics: clear 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 that exerts a myorelaxant effect.

In vitro studies show that thiocolchicoside binds exclusively to GABA and strychnine-sensitive glycine receptors. Acting as a GABA receptor antagonist, thiocolchicoside produces an effective myorelaxant effect via regulatory complex mechanisms at the supraspinal level, although its glycinergic 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.

Moreover, electroencephalographic studies have shown that thiocolchicoside and its major metabolite do not produce a sedative effect.

Pharmacokinetics.

Absorption.

After intramuscular administration, maximum plasma concentration (Cmax) of thiocolchicoside is observed within 30 minutes; plasma levels of 113 ng/mL are reached after a 4 mg dose and 175 ng/mL after an 8 mg dose. Corresponding values of the area under the plasma concentration-time curve (AUC) are 283 ng·h/mL 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 an 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 the plasma clearance is 19.2 L/h.

Clinical characteristics.

Indications.

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

Contraindications.

Thiocolchicoside should not be used:

• in patients with hypersensitivity to the active substance or to any of the excipients of the medicinal product;
• in patients suffering from flaccid paralysis, muscle hypotonia;
• during the entire pregnancy period;
• during breastfeeding;
• in women of childbearing potential who are not using adequate contraceptive methods during treatment with the medicinal product Tiovista and for one month after discontinuation of treatment;
• in men who are not using adequate contraceptive methods during treatment with the medicinal product Tiovista and for three months after discontinuation of treatment.

Interaction with other medicinal products and other forms of interaction.

Information regarding interactions is lacking.

Special precautions for use.

Vasovagal syncope has been reported after intramuscular injection of thiocolchicoside; therefore, patients should be monitored following administration of the medicinal product (see section "Adverse reactions").

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

Epileptic seizures may occur during treatment with thiocolchicoside in patients with epilepsy or 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 preclinical study data, one of the metabolites of thiocolchicoside, SL59.0955, causes aneuploidy (a change in the number of chromosomes in dividing cells) at concentrations close to those achieved with oral administration of 8 mg twice daily, 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. To prevent these risks, 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 the need to use effective contraceptive methods.

Reactions at the injection site

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

Important information about excipients

The medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., essentially "sodium-free".

Use during pregnancy or breastfeeding

Contraception in women and men

Thiocolchicoside is contraindicated in women of childbearing potential and in men who are not using effective contraception (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 have aneugenic effects at various concentration levels, which represents a risk factor for human fertility.

Ability to influence the ability to drive and use machines

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 injection.

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 precautions for use").

Children.

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

Overdose.

Symptoms. There is no data regarding cases of overdose.

Treatment. In case 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 (≥ 1/10000 – < 1/1000), very rare (< 1/10000), frequency not known (cannot be estimated from available data).

Immune system disorders:

uncommon – pruritus; rare – urticaria; very rare – arterial hypotension; frequency not known – angioedema and anaphylactic reactions, including anaphylactic shock.

Nervous system disorders:

common – somnolence; rare – excitement or brief confusion; frequency not known – 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, abdominal pain; uncommon – nausea, vomiting; rare – heartburn.

Hepatobiliary disorders:

frequency not known – liver injury (see section "Special precautions for use").

Skin and subcutaneous tissue disorders:

uncommon – allergic skin reactions.

General disorders and administration site conditions:

frequency not known: injection site reactions, including swelling, erythema, pruritus, pain around the injection site, and Nicolau syndrome ("drug 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 ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and pharmacists, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua

Shelf life.

4 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging.

2 ml in a vial; 6 vials in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

VEM Ilac San. ve Tic. A.S.

Manufacturer's address and site of operations.

Cerkezkoy Organize Sanayi Bolgesi, Karaagac Mahallesi, Fatih Boulevard No: 38 Kapaklı/Tekirdag /Turkey.