Relamio

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

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 properties: 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 with muscle relaxant properties.

In in vitro studies, thiocolchicoside binds only to GABA and strychnine-sensitive glycine receptors. Acting as a GABA receptor antagonist, thiocolchicoside exerts an effective myorelaxant effect via regulatory complex mechanisms at the supraspinal level, although its glycine-mediated mechanism of action cannot be excluded.

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

In in vivo studies, the muscle relaxant properties of thiocolchicoside and its main metabolite have been demonstrated 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 (Cmax) of thiocolchicoside is reached within 30 minutes, with levels of 113 ng/mL achieved after a 4 mg dose and 175 ng/mL after an 8 mg dose. Corresponding values for 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 observed at lower concentrations, with a Cmax of 11.7 ng/mL reached 5 hours after administration of the dose, 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 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 or muscle hypotonia;
• during pregnancy and breastfeeding;
• in women of childbearing potential who are not using appropriate contraceptive methods during treatment with Relamio and for one month after discontinuation of treatment;
• in men who are not using appropriate contraceptive methods during treatment with Relamio and for three months after discontinuation of treatment.

Interaction with other medicinal products and other forms of interaction

Information on interactions is lacking.

Special precautions for use

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

Hepatic injury associated with the use of thiocolchicoside has been reported in the post-marketing period. 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 develop during treatment with the medicinal product, therapy should be discontinued and medical advice sought (see section "Adverse reactions").

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 dose of thiocolchicoside, 8 mg per day, must 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 approaching those achieved with 8 mg twice daily oral administration, which may similarly affect humans.

Aneuploidy is considered a risk factor for teratogenicity, embryotoxicity/fetotoxicity, miscarriage, altered fertility in men, and potential carcinogenic risk. 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 contraception.

Reactions at the injection site

Reactions at the injection site have been reported after 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 on 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. 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 an aneugenic effect at various concentration levels, which represents a risk factor for impaired human fertility.

Ability to influence reaction speed 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.

Method of Administration and Dosage

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 administration should be avoided (see section "Special Instructions").

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.

Side effects

The following adverse reactions are classified according to MedDRA system organ classes and frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), frequency not known (cannot be estimated from the 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").

Gastrointestinal disorders:

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

Hepatobiliary disorders:

Frequency not known – hepatic injury (see section "Special precautions").

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 ("skin embolization" and "livedoid dermatitis") following intramuscular injection.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, 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 location of operations

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