Muscomed

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

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 exclusively 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 various 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 have also shown that thiocolchicoside and its major metabolite do not produce a sedative effect.

Pharmacokinetics

Absorption

After intramuscular administration, maximum plasma concentration (C_max) 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 values of the area under the pharmacokinetic curve (AUC) are 283 and 417 ng·h/mL, respectively.

The pharmacologically active metabolite SL18.0740 is also detected at lower concentrations, with a C_max of 11.7 ng/mL reached 5 hours after administration, 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.

Adjunctive therapy for painful muscle spasms associated with 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 therapy;
• use in men who are not using appropriate contraceptive measures during treatment and for three months after completion of therapy.

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 following administration of the medicinal product (see section "Adverse reactions").

During the post-marketing period, hepatic adverse events associated with the use of thiocolchicoside have 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 with epilepsy or other 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, changes in male fertility, and as 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 potential risks to a possible pregnancy and about the need to use effective contraception.

Following intramuscular administration of thiocolchicoside, injection site reactions have been reported, 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.

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

Use during pregnancy or breastfeeding.

Contraception in women and men.

The medicinal product is contraindicated in women of childbearing potential and in men who do not use 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; 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 while 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 in children under 16 years of age.

Overdose

There are no data on 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), and not known (frequency cannot be estimated from available data).

Immune system disorders:

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

Nervous system disorders:

Common – somnolence; rare – excitation or brief confusion; not known – malaise, with or without vasovagal syncope within the first few minutes after intramuscular injection; seizures (see section "Special Warnings and Precautions for Use").

Gastrointestinal disorders:

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

Hepatobiliary disorders:

Frequency not known – liver injury (see section "Special Warnings and Precautions for Use").

Skin and subcutaneous tissue disorders:

Uncommon – allergic skin reactions.

General disorders and administration site conditions:

Not known – 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 professionals and patients, as well as their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: 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 category.

Prescription only.

Manufacturer.

UORLID MEDITSIN ILACH SAN. VE TIDJ. A.SH./
WORLD MEDICINE ILAC SAN. VE TIC. A.S.

Manufacturer's address and location of operations.

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

Marketing Authorization Holder.

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